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Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer

BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), whi...

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Autores principales: Pei, Nana, Mao, Yingying, Wan, Pengfei, Chen, Xinglu, Li, Andrew, Chen, Huiying, Li, Jinlong, Wan, Renqiang, Zhang, Yanling, Du, Hongyan, Chen, Baihong, Jiang, Guangyu, Xia, Minghan, Sumners, Colin, Hu, Guixue, Gu, Dongsheng, Li, Hongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466725/
https://www.ncbi.nlm.nih.gov/pubmed/28599664
http://dx.doi.org/10.1186/s13046-017-0542-0
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author Pei, Nana
Mao, Yingying
Wan, Pengfei
Chen, Xinglu
Li, Andrew
Chen, Huiying
Li, Jinlong
Wan, Renqiang
Zhang, Yanling
Du, Hongyan
Chen, Baihong
Jiang, Guangyu
Xia, Minghan
Sumners, Colin
Hu, Guixue
Gu, Dongsheng
Li, Hongwei
author_facet Pei, Nana
Mao, Yingying
Wan, Pengfei
Chen, Xinglu
Li, Andrew
Chen, Huiying
Li, Jinlong
Wan, Renqiang
Zhang, Yanling
Du, Hongyan
Chen, Baihong
Jiang, Guangyu
Xia, Minghan
Sumners, Colin
Hu, Guixue
Gu, Dongsheng
Li, Hongwei
author_sort Pei, Nana
collection PubMed
description BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs. RESULTS: In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated. Viral vector mediated overexpression of AT2R induced apoptosis and dramatically suppressed BCa cell proliferation in vitro, suggesting a therapeutic effect. Investigation into the mechanism revealed that the overexpression of AT2R increases the expression levels of caspase-3, caspase-8, and p38 and decreases the expression level of pErk. AT2R overexpression also leads to upregulation of 2 apoptosis-related genes (BCL2A1, TNFSF25) and downregulation of 8 apoptosis-related genes (CASP 6, CASP 9, DFFA, IGF1R, PYCARD, TNF, TNFRSF21, TNFSF10, NAIP) in transduced EJ cells as determined by PCR Array analysis. In vivo, we observed that AT2R overexpression caused significant reduction in xenograft tumors sizes by downregulation VEGF and induction of apoptosis. CONCLUSIONS: Taken together, the data suggest that AT1R, AT2R or Mas could be used as a diagnostic marker of BCa and AT2R is a promising novel target gene for BCa gene therapy.
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spelling pubmed-54667252017-06-14 Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer Pei, Nana Mao, Yingying Wan, Pengfei Chen, Xinglu Li, Andrew Chen, Huiying Li, Jinlong Wan, Renqiang Zhang, Yanling Du, Hongyan Chen, Baihong Jiang, Guangyu Xia, Minghan Sumners, Colin Hu, Guixue Gu, Dongsheng Li, Hongwei J Exp Clin Cancer Res Research BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs. RESULTS: In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated. Viral vector mediated overexpression of AT2R induced apoptosis and dramatically suppressed BCa cell proliferation in vitro, suggesting a therapeutic effect. Investigation into the mechanism revealed that the overexpression of AT2R increases the expression levels of caspase-3, caspase-8, and p38 and decreases the expression level of pErk. AT2R overexpression also leads to upregulation of 2 apoptosis-related genes (BCL2A1, TNFSF25) and downregulation of 8 apoptosis-related genes (CASP 6, CASP 9, DFFA, IGF1R, PYCARD, TNF, TNFRSF21, TNFSF10, NAIP) in transduced EJ cells as determined by PCR Array analysis. In vivo, we observed that AT2R overexpression caused significant reduction in xenograft tumors sizes by downregulation VEGF and induction of apoptosis. CONCLUSIONS: Taken together, the data suggest that AT1R, AT2R or Mas could be used as a diagnostic marker of BCa and AT2R is a promising novel target gene for BCa gene therapy. BioMed Central 2017-06-09 /pmc/articles/PMC5466725/ /pubmed/28599664 http://dx.doi.org/10.1186/s13046-017-0542-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Pei, Nana
Mao, Yingying
Wan, Pengfei
Chen, Xinglu
Li, Andrew
Chen, Huiying
Li, Jinlong
Wan, Renqiang
Zhang, Yanling
Du, Hongyan
Chen, Baihong
Jiang, Guangyu
Xia, Minghan
Sumners, Colin
Hu, Guixue
Gu, Dongsheng
Li, Hongwei
Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title_full Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title_fullStr Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title_full_unstemmed Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title_short Angiotensin II type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
title_sort angiotensin ii type 2 receptor promotes apoptosis and inhibits angiogenesis in bladder cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466725/
https://www.ncbi.nlm.nih.gov/pubmed/28599664
http://dx.doi.org/10.1186/s13046-017-0542-0
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